Neuromuscular stimulation ameliorates ischemia-induced walking impairment in the rat claudication model
- 49 Downloads
Intermittent claudication (IC) is the most common symptom of peripheral arterial disease which significantly deteriorates the quality of life of patients. Exercise training is by far the most effective treatment for IC; however, the underlying mechanisms remain elusive. To determine the local mechanisms by which exercise training improves walking performance in claudicants, we developed an implantable device to locally induce ischemic skeletal muscle contraction mimicking exercise via electrical stimulation (ES). Rats were assigned to four groups, Sham, Ischemia (Isch), Isch + exercise and Isch + ES groups. Following both unilateral femoral and iliac artery occlusion, rats showed sustained impairment of walking performance in the treadmill test. Chronic low-frequency ES of ischemic skeletal muscles for 2 weeks significantly recovered the occlusion-induced walking impairment in the rat claudication model. We further analyzed the ischemic skeletal muscles immunohistochemically following ES or exercise training; both ES and exercise training significantly increased capillaries in the ischemic skeletal muscles and shifted the muscle fibers toward oxidative types. These findings demonstrate that ES takes on common features of exercise in the rat claudication model, which may facilitate investigations on the local mechanisms of exercise-induced functional recovery.
KeywordsIntermittent claudication Exercise Electrical stimulation Skeletal muscle Mechanism
The authors thank Jun Harada for the scientific counsel.
Momoko Shiragaki-Ogitani: conceptualization, formal analysis, investigation, and writing—original draft. Keita Kono: writing—original draft. Futhoshi Nara: conceptualization and writing—original draft. Atsushi Aoyagi: conceptualization, formal analysis, investigation, and writing—original draft.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Daiichi Sankyo Co., Ltd.
- 6.Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA et al (2017) 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 135:e726–e779PubMedGoogle Scholar
- 11.Watson L, Ellis B, Leng GC (2008) Exercise for intermittent claudication. Cochrane Database Syst Rev 4:CD000990Google Scholar
- 13.Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER, Cohen DJ et al (2012) Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation 125:130–139PubMedCrossRefGoogle Scholar
- 14.Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA et al (2003) Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 107:3109–3116PubMedCrossRefGoogle Scholar
- 36.Dreibati B, Lavet C, Pinti A, Poumarat G (2010) Influence of electrical stimulation frequency on skeletal muscle force and fatigue. Ann Phys Rehabil Med 53(266–271):271–287Google Scholar
- 47.Englund EK, Langham MC, Ratcliffe SJ, Fanning MJ, Wehrli FW et al (2015) Multiparametric assessment of vascular function in peripheral artery disease: dynamic measurement of skeletal muscle perfusion, blood-oxygen-level dependent signal, and venous oxygen saturation. Circ Cardiovasc Imaging 8:e002673PubMedCrossRefGoogle Scholar